Dionysios Papaioannou

Convenient synthesis of n-trityl-o-alkyl-l-hydroxyamino acids and derivatives : Application to the synthesis of related peptides

Abstract The disodium salts of N-trityl-hydroxyamino acids 2 prepared in situ with NaH, in the presence of imidazole, were selectively alkylated with alkyl iodides to give N-trityl-O-alkyl-hydroxyamino acids 3 . Compounds 3 were readily converted to O-alkyl-hydroxyamino acids 5 or other intermediates useful for incorporation into a peptide chain. The applicability of these derivatives in the preparation of related peptides is illustrated by the synthesis of the protected analogues of enkephalin N-carbobenzoxy-tyrosyl-glycyl-glycyl-phenylalanyl-(O-ethyl) serine benzyl ester and N-carbobenzoxy-tyrosyl-glycyl-glycyl-phenylalanyl-(O-methyl) homoserine benzyl ester.

Preparation of spermine conjugates with acidic retinoids with potent ribonuclease P inhibitory activity.

Novel mono- and diacylated spermines, readily obtained using isolable succinimidyl active esters of acidic retinoids for the selective acylation of free spermine or in situ activated acidic retinoids for acylating selectively protected spermine followed by deprotection, were shown to inhibit the ribozyme ribonuclease P more strongly than the parent retinoids.

Effect of conjugates of all-trans-retinoic acid and shorter polyene chain analogues with amino acids on prostate cancer cell growth

In the present work, a series of conjugates of amino acids with all-trans-retinoic acid (ATRA) and shorter polyene chain analogues were rationally designed, synthesized by coupling the succinimidyl active esters of the acidic retinoids with appropriately protected amino acids or peptides followed by deprotection, and examined for their possible effect on viability of human prostate cancer LNCaP cells. In contrast to ATRA, all conjugates bearing amino acids with polar side chains showed no inhibitory effect on LNCaP cell proliferation, while conjugates with alpha-amino acids with lipophilic side chain, such as 7, or linear amino acids, such as 9, significantly decreased prostate cancer LNCaP cell number. Interestingly, while the effect of ATRA was RARalpha-dependent, the effect of its active analogues was not inhibited by a selective RARalpha antagonist. Cell cycle analysis showed no effect on cell cycle, while quantitative analysis by annexin V-propidium iodide staining revealed that neither ATRA nor its analogues affected LNCaP cell apoptosis or necrosis. These results demonstrate that compounds 7 and 9 are potentially useful agents that warrant further preclinical development for treatment of prostate cancer.

Phenol oxidation and biosynthesis. Part 26. Isonitriles in the synthesis of benzylisoquinoline derivatives

Lithiomethyl and toluene-4-sulphonyl(potassiomethyl)isonitriles have been applied in short high-yield homologations of O-benzylvanillin, O-benzylisovanillin, and veratraldehyde giving N-(2-arylethyl)-2-arylacetamides and subsequently isoquinoline derivatives. These experiments are relevant to the preparation of alkaloids including papaverine and reticuline.

Phenol oxidation and biosynthesis. Part 27. Reactions of relevance to the formation of erysodienone in vitro

Potassium hexacyanoferrate(III) oxidation of N-(2-arylethyl)-2-arylacetamide and arylmethyl arylpropyl ketone gave the corresponding nine-membered ring derivatives formed by p,p-phenol oxidative coupling (where aryl was 3-hydroxy-4-methoxyphenyl). This strongly supports the previously reported mechanism for the in vitro formation of erysodienone. The required ketone was prepared from O-benzylisovanillin by homologation with toluene-4-sulphonylmethyl isonitrile.

Preparation of optically active cyclic ether derivatives of amino acids and peptides

Treatment of N-tritylmethioninol (1) or peptides (6), incorporating methionyl and amino alcohol residues, with Mel, followed by base mediated cyclisation of the thus derived sulphonium salts, provides the title compounds in excellent yields.

Simple syntheses of (S)-2- and 4-amino-5-hydroxypentanoic acids

The title compounds were efficiently prepared by selective reductions of α- and γ-methyl (S)-N-tritylglutamates with LiAlH4

Synthesis and chemical modification of homoseryl peptides

The readily synthesised N,O-ditritylhomoserine (4) was used for the efficient incorporation of homoserine (1) into peptides; the derived homoseryl peptides were transformed into peptides of canaline and 1,4-diaminobutyric acid using the Mitsunobu reaction.